scholarly journals Neural Defects Caused by Total and Wnt1-Cre Mediated Ablation of p120ctn in Mice

2020 ◽  
Author(s):  
Tim Pieters ◽  
Ellen Sanders ◽  
Huiyu Tian ◽  
Jolanda van Hengel ◽  
Frans Van Roy
Keyword(s):  
Cell Adhesion ◽  
Neural Tube ◽  
Tube Formation ◽  
Neural Tube Closure ◽  
Actin Binding ◽  
Apical Side ◽  
Developmental Role ◽  
Tube Closure ◽  
Neural Tube Formation

Abstract Background p120 catenin (p120ctn) is an important component in the cadherin-catenin cell adhesion complex because it stabilizes cadherin-mediated intercellular junctions. Outside these junctions, p120ctn is actively involved in the regulation of small GTPases of the Rho family, in actomyosin dynamics and in transcription regulation. We and others reported that loss of p120ctn in mouse embryos results in an embryonic lethal phenotype, but the exact developmental role of p120ctn during brain formation has not been reported.Results We used Cre/loxP technology to achieve full or tissue-specific deletion of p120ctn in the developing embryo. We combined floxed p120ctn mice with Del-Cre or Wnt1-Cre mice to deplete p120ctn from either all cells or specific brain and neural crest cells. Complete loss of p120ctn in mid-gestation embryos resulted in an aberrant morphology, including growth retardation, failure to switch from lordotic to fetal posture, and defective neural tube formation and neurogenesis. By expressing a wild-type p120ctn from the ROSA26 locus in p120ctn-null mouse embryonic stem cells, we could recapitulate neurogenesis and partially rescue neurogenesis. To further investigate the developmental role of p120ctn in neural tube formation, we generated conditional p120ctnfl/fl;Wnt1Cre knockout mice. p120ctn deletion in Wnt1-expressing cells resulted in neural tube closure defects (NTDs) and craniofacial abnormalities. These defects could not be correlated with misregulation of brain marker genes or cell proliferation. In contrast, we found that p120ctn is required for proper expression of the cell adhesion components N-cadherin, E-cadherin and β-catenin, and of actin-binding proteins cortactin and Shroom3 at the apical side of neural folds. This region is of critical importance for closure of neural folds. Surprisingly, the lateral side of mutant neural folds showed loss of p120ctn, but not of N-cadherin, β-catenin or cortactin.Conclusions These results indicate that p120ctn is strictly required for neurogenesis and neurulation. Elimination of p120ctn in cells expressing Wnt1 affects neural tube closure by hampering correct formation of specific adhesion and actomyosin complexes at the apical side of neural folds. Collectively, our results demonstrate the crucial role of p120ctn during brain morphogenesis.

scholarly journals Neural defects caused by total and Wnt1-Cre mediated ablation of p120ctn in mice

2020 ◽  
Author(s):  
Tim Pieters ◽  
Ellen Sanders ◽  
Huiyu Tian ◽  
Jolanda van Hengel ◽  
Frans Van Roy
Keyword(s):  
Cell Adhesion ◽  
Neural Tube ◽  
Tube Formation ◽  
Neural Tube Closure ◽  
Actin Binding ◽  
Apical Side ◽  
Developmental Role ◽  
Tube Closure ◽  
Neural Tube Formation

Abstract Background p120 catenin (p120ctn) is an important component in the cadherin-catenin cell adhesion complex because it stabilizes cadherin-mediated intercellular junctions. Outside these junctions, p120ctn is actively involved in the regulation of small GTPases of the Rho family, in actomyosin dynamics and in transcription regulation. We and others reported that loss of p120ctn in mouse embryos results in an embryonic lethal phenotype, but the exact developmental role of p120ctn during brain formation has not been reported. Results We combined floxed p120ctn mice with Del-Cre or Wnt1-Cre mice to deplete p120ctn from either all cells or specific brain and neural crest cells. Complete loss of p120ctn in mid-gestation embryos resulted in an aberrant morphology, including growth retardation, failure to switch from lordotic to fetal posture, and defective neural tube formation and neurogenesis. By expressing a wild-type p120ctn from the ROSA26 locus in p120ctn-null mouse embryonic stem cells, we could partially rescue neurogenesis. To further investigate the developmental role of p120ctn in neural tube formation, we generated conditional p120ctn fl/fl ;Wnt1Cre knockout mice. p120ctn deletion in Wnt1-expressing cells resulted in neural tube closure defects (NTDs) and craniofacial abnormalities. These defects could not be correlated with misregulation of brain marker genes or cell proliferation. In contrast, we found that p120ctn is required for proper expression of the cell adhesion components N-cadherin, E-cadherin and β-catenin, and of actin-binding proteins cortactin and Shroom3 at the apical side of neural folds. This region is of critical importance for closure of neural folds. Surprisingly, the lateral side of mutant neural folds showed loss of p120ctn, but not of N-cadherin, β-catenin or cortactin. Conclusions These results indicate that p120ctn is required for neurogenesis and neurulation. Elimination of p120ctn in cells expressing Wnt1 affects neural tube closure by hampering correct formation of specific adhesion and actomyosin complexes at the apical side of neural folds. Collectively, our results demonstrate the crucial role of p120ctn during brain morphogenesis.

The role of F-cadherin in localizing cells during neural tube formation in Xenopus embryos

Development ◽  
1998 ◽  
Vol 125 (2) ◽  
pp. 301-312 ◽  
Author(s):  
A. Espeseth ◽  
G. Marnellos ◽  
C. Kintner
Keyword(s):  
Cell Adhesion ◽  
Neural Tube ◽  
Cell Adhesion Molecule ◽  
Ectopic Expression ◽  
Tube Formation ◽  
Cell Movements ◽  
Xenopus Embryos ◽  
Extensive Cell ◽  
Neural Tube Formation

The cell adhesion molecule F-cadherin is expressed in Xenopus embryos at boundaries that subdivide the neural tube into different regions, including one, the sulcus limitans, which partitions the caudal neural tube into a dorsal and ventral half (alar and basal plate, respectively). Here we examine the role of F-cadherin in positioning cells along the caudal neuraxis during neurulation. First, we show that ectopic expression of F-cadherin restricts passive cell mixing within the ectodermal epithelium. Second, we show that F-cadherin is first expressed at the sulcus limitans prior to the extensive cell movements that accompany neural tube formation, suggesting that it might serve to position cells at the sulcus limitans by counteracting their tendency to disperse during neurulation. We test this idea using an assay that measures changes in cell movements during neurulation in response to differential cell adhesion. Using this assay, we show that cells expressing F-cadherin localize preferentially to the sulcus limitans, but still disperse when located away from the sulcus limitans. In addition, inhibiting cadherin function prevents cells from localizing precisely at the sulcus limitans. These results indicate that positioning of cells at the sulcus limitans is mediated in part by the differential expression of F-cadherin.

scholarly journals Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds

Development ◽  
2021 ◽  
Vol 148 (2) ◽  
pp. dev195008
Author(s):  
Izabela Kowalczyk ◽  
Chanjae Lee ◽  
Elisabeth Schuster ◽  
Josefine Hoeren ◽  
Valentina Trivigno ◽  
...  
Keyword(s):  
Neural Tube ◽  
Planar Cell Polarity ◽  
Adaptor Proteins ◽  
Tube Formation ◽  
Neural Tube Closure ◽  
Model Organisms ◽  
Loss Of Function ◽  
Functional Interaction ◽  
Apical Constriction ◽  
Tube Closure

ABSTRACTPathogenic mutations in the endocytic receptor LRP2 in humans are associated with severe neural tube closure defects (NTDs) such as anencephaly and spina bifida. Here, we have combined analysis of neural tube closure in mouse and in the African Clawed Frog Xenopus laevis to elucidate the etiology of Lrp2-related NTDs. Lrp2 loss of function impaired neuroepithelial morphogenesis, culminating in NTDs that impeded anterior neural plate folding and neural tube closure in both model organisms. Loss of Lrp2 severely affected apical constriction as well as proper localization of the core planar cell polarity (PCP) protein Vangl2, demonstrating a highly conserved role of the receptor in these processes, which are essential for neural tube formation. In addition, we identified a novel functional interaction of Lrp2 with the intracellular adaptor proteins Shroom3 and Gipc1 in the developing forebrain. Our data suggest that, during neurulation, motifs within the intracellular domain of Lrp2 function as a hub that orchestrates endocytic membrane removal for efficient apical constriction, as well as PCP component trafficking in a temporospatial manner.

scholarly journals Meroanencephaly in an English Pointer Neonate

2020 ◽  
Vol 48 ◽  
Author(s):  
Luisa Mariano Cerqueira da Silva ◽  
Helena Piúma Gonçalves ◽  
Thaís Cozza Dos Santos ◽  
Clarissa Caetano De Castro ◽  
Cristina Gevehr Fernandes ◽  
...  
Keyword(s):  
Neural Tube ◽  
Spontaneous Breathing ◽  
Tube Formation ◽  
Neural Tube Closure ◽  
Parietal Region ◽  
Skull Bone ◽  
Cranial Cavity ◽  
Brain Malformations ◽  
Macroscopic Examination ◽  
Tube Closure

Background: Malformations are structural or functional abnormalities in the organs and structures present at birth. These conditions are rarely described in the newborns of dogs and can lead to their death. Meroanencephaly is a defect of the neural tube closure malformation. This study aims to characterize the clinical-pathological aspects of neonatal meroanencephaly since brain malformations are rare in newborn dogs.Case: A two-day-old English Pointer canine was sent for a necropsy. The newborn belonged to a litter of eight puppies, and only this one had macroscopic cranial alterations. Another puppy that died as a consequence of being trampled by the bitch was also necropsied. The newborn was alive for 48 h until death and presented apathy, crying, sucking reflex and opisthotonus. Macroscopic examination of the baby revealed flattening of the skull, with a slit at the site of bone symphysis fusion, and a slit in the skin of the parietal region, covered by thin, translucent meningeal tissue. The heads of the two animals were examined by radiography to identify the features of anencephaly in one of the animals by visualizing skull bone flattening. Upon removing the skin and exposing the cranial cavity, an irregular reddish mass was revealed, that corresponded microscopically to area cerebrovasculosa, composed of neurons, rudimentary glial tissue, vascular neoformations, as well as hemorrhagic areas.Discussion: Meroanencephaly is a type of anencephaly, a congenital malformation originating from abnormal neurulation, which results from the absence of neural fold fusion during neural tube formation. Live-born anencephalics have some brainstem-driven functions such as spontaneous breathing and some reflex responses, for instance, suction. Several genetic or teratogenic factors, such as viruses, radiation, drugs administered during pregnancy and other pathologies transmitted from bitch to fetus, can lead to this defect. The reports on anatomopathological findings and the presence of area cerebrovasculosa are rare.

scholarly journals A requirement for NF-protocadherin and TAF1/Set in cell adhesion and neural tube formation

2006 ◽  
Vol 291 (1) ◽  
pp. 170-181 ◽  
Author(s):  
Dana Rashid ◽  
Katie Newell ◽  
Leah Shama ◽  
Roger Bradley
Keyword(s):  
Cell Adhesion ◽  
Neural Tube ◽  
Tube Formation ◽  
Neural Tube Formation

scholarly journals Role of Mammalian Formin Fhod3 in Neural Tube Closure

2018 ◽  
Vol WCP2018 (0) ◽  
pp. PO4-1-52
Author(s):  
Hikmawan W Sulistomo ◽  
Yohko Kage ◽  
Takayuki Nemoto ◽  
Ryu Takeya
Keyword(s):  
Neural Tube ◽  
Neural Tube Closure ◽  
Tube Closure

scholarly journals Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies

2018 ◽  
Vol 6 (3) ◽  
pp. 22 ◽  
Author(s):  
Diana Juriloff ◽  
Muriel Harris
Keyword(s):  
Neural Tube ◽  
Gene Mutations ◽  
Neural Tube Closure ◽  
Specific Gene ◽  
New Developments ◽  
Mouse Mutants ◽  
Folate Pathway ◽  
Tube Closure ◽  
Anterior Posterior

The human neural tube defects (NTD), anencephaly, spina bifida and craniorachischisis, originate from a failure of the embryonic neural tube to close. Human NTD are relatively common and both complex and heterogeneous in genetic origin, but the genetic variants and developmental mechanisms are largely unknown. Here we review the numerous studies, mainly in mice, of normal neural tube closure, the mechanisms of failure caused by specific gene mutations, and the evolution of the vertebrate cranial neural tube and its genetic processes, seeking insights into the etiology of human NTD. We find evidence of many regions along the anterior–posterior axis each differing in some aspect of neural tube closure—morphology, cell behavior, specific genes required—and conclude that the etiology of NTD is likely to be partly specific to the anterior–posterior location of the defect and also genetically heterogeneous. We revisit the hypotheses explaining the excess of females among cranial NTD cases in mice and humans and new developments in understanding the role of the folate pathway in NTD. Finally, we demonstrate that evidence from mouse mutants strongly supports the search for digenic or oligogenic etiology in human NTD of all types.

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